Efficacious anti-cd26 antibody biomarker

Abstract

Potential prognostic biomarkers for CD26-targeted therapy were identified based on phase I study data of a humanized anti-CD26 monoclonal antibody YS110 against CD26-expressing tumors. Using boxplot analysis, scatter plot analysis, Pearson's product-moment correlation/Spearman's rank-difference correlation, bar graph analysis, and receiver operating characteristic (ROC), a correlation between soluble CD26 titer variation and tumor volume variation by YS110 administration, RECIST criteria evaluation, and progression-free survival (PFS) were examined. Further, mechanism of serum soluble CD26 titer variation was confirmed by in vitro experiments. As a result, serum soluble CD26/DPP4 titer variation at an early stage of YS110 treatment was found for the first time as a predictive biomarker to evaluate a therapeutic effect.

1 . A method for selecting a cancer patient that have a potential to obtain a therapeutic effect with an anti-CD26 antibody, the method comprising:
 comparing a level of soluble CD26 in serum of the patient before a reference administration of an anti-CD26 antibody with the level of soluble CD26 in the serum of the patient on a measurement date; and   when the level of soluble CD26 in the serum of the patient on the measurement date is less than 85% of the level of soluble CD26 in the serum of the patient before the reference administration, selecting the patient as having the potential to obtain a therapeutic effect with the anti-CD26 antibody, wherein   the measurement date is Day 1 to Day 60 with a reference administration date as Day 1, and   the patient is a patient to whom the anti-CD26 antibody is administered at least once as a reference administration, and   when the measurement date corresponds to an administration date of the anti-CD26 antibody, the level of soluble CD26 in the serum of the patient on the measurement date is the level of soluble CD26 in the serum of the patient before the administration of the anti-CD26 antibody on the measurement date.   
     
     
         2 . The method according to  claim 1 , wherein when the measurement date is Day 1 to Day 30 from the reference administration, and the level of soluble CD26 in the serum of the patient on the measurement date is less than 60% of the level of soluble CD26 in the serum of the patient before the reference administration, the patient is selected as having the potential to obtain a therapeutic effect with the anti-CD26 antibody. 
     
     
         3 . The method according to  claim 1 , wherein when the measurement date is Day 22 to Day 30 from the reference administration, and the level of soluble CD26 in the serum of the patient on the measurement date is less than 60% of the level of soluble CD26 in the serum of the patient before the reference administration, the patient is selected as having the potential to obtain a therapeutic effect with the anti-CD26 antibody. 
     
     
         4 . The method according to  claim 1 , wherein when the measurement date is Day 2 to Day 8 from the reference administration, and the level of soluble CD26 in the serum of the patient on the measurement date is less than 50% of the level of soluble CD26 in the serum of the patient before the reference administration, the patient is selected as having the potential to obtain a therapeutic effect with the anti-CD26 antibody. 
     
     
         5 . The method according to  claim 1 , wherein
 when the patient is a patient to whom the anti-CD26 antibody is administered with a frequency of once every two weeks, and   the measurement date is Day 22 to Day 30 from the reference administration, and   the level of soluble CD26 in the serum of the patient on the measurement date is less than 65% of the level of soluble CD26 in the serum of the patient before the reference administration, the patient is selected as having the potential to obtain a therapeutic effect with the anti-CD26 antibody.   
     
     
         6 . The method according to  claim 1 , wherein
 when the patient is a patient to whom the anti-CD26 antibody is administered with a frequency of once every two weeks, and   the measurement date is Day 29 from the reference administration, and   the level of soluble CD26 in the serum of the patient on the measurement date is less than 62.3% of the level of soluble CD26 in the serum of the patient before the reference administration, the patient is selected as having the potential to obtain a therapeutic effect with the anti-CD26 antibody.   
     
     
         7 . The method of  claim 5 , wherein the patient is male. 
     
     
         8 . The method according to  claim 1 , wherein
 when the patient is a patient to whom the anti-CD26 antibody is administered with a frequency of once a week, and   the measurement date is Day 2 to Day 8 from the reference administration, and   the level of soluble CD26 in the serum of the patient on the measurement date is less than 50% of the level of soluble CD26 in the serum of the patient before the reference administration, the patient is selected as having the potential to obtain a therapeutic effect with the anti-CD26 antibody.   
     
     
         9 . The method according to  claim 8 , wherein when the level of soluble CD26 in the serum of the patient on the measurement date is less than 49% of the level of soluble CD26 in the serum of the patient before the reference administration, the patient is selected as having the potential to obtain a therapeutic effect with the anti-CD26 antibody. 
     
     
         10 . The method according to  claim 1 , wherein
 when the patient is a patient to whom the anti-CD26 antibody is administered with a frequency of once a week, and   the measurement date is on or after Day 15 from reference administration, and   the level of soluble CD26 in the serum of the patient on the measurement date is less than 30% of the level of soluble CD26 in the serum of the patient before the reference administration, the patient is selected as having the potential to obtain a therapeutic effect with the anti-CD26 antibody.   
     
     
         11 . The method of  claim 10 , wherein when the level of soluble CD26 in the serum of the patient on the measurement date is less than 26% of the level of soluble CD26 in the serum of the patient before the reference administration, the patient is selected as having the potential to obtain a therapeutic effect with the anti-CD26 antibody. 
     
     
         12 . The method of  claim 8 , wherein the patient is a patient to whom 6 mg/kg of the anti-CD26 antibody is administered. 
     
     
         13 - 46 . (canceled) 
     
     
         47 . The method according to  claim 1 , wherein the patient is a patient to whom the anti-CD26 antibody is administered at a frequency of once every two weeks or once a week. 
     
     
         48 . The method of  claim 1 , wherein the anti-CD26 antibody is YS110. 
     
     
         49 . The method of  claim 1 , wherein the cancer is malignant mesothelioma.